P1304: TREATMENT WITH COMBINATION OF RITUXIMAB AND INTRAVENOUS Γ GLOBULIN IS EFFECTIVE IN PROMOTING ENGRAFTMENT IN DONOR SPECIFIC ANTIBODY POSITIVE PATIENTS RECEIVING HAPLOIDENTICAL STEM CELL TRANSPLANT
Authors: Yuyan Shen, Lining Zhang, Xiaoyu Zhang, Jialin Wei, Sizhou Feng, Mingzhe Han, Yi He, Rongli Zhang, Erlie Jiang
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Donor-specific anti-HLA antibodies(DSAs) are a major cause of engraftment failure in patients receiving haploidentical stem cell transplantation(HaploSCT). Effective procedures are needed for those who demand urgent transplantation and have no other donor options. We here report thirteen patients successfully treated with desensitization of rituximab and intravenous γ globulin all achieved neutrophil engraftment after haploHSCT. Aims: There is emerging researches trying different combinations of therapies to remove HLA antibody before HaploSCT. We here retrospectively report a positive result of using combination of only rituximab and IVIG. Methods: Data of hematologic malignancy and aplastic anemia patients, median age of 42 years (range 25~53 years),with DSA who received combination desensitization of rituximab and intravenous γ globulin prior to HaploSCT from March 2017 to July 2022 at Institute of Hematology & Blood Diseases hospital were included in this research group, All patients received unmanipulated HaploSCT. Grafts were all peripheral stem cells. All thirteen patients were with DSA MFI >4000. Patients were treated with one (n=3) or two(n=10) doses of rituximab(375mg/m2), All patients received at least one dose of rituximab at the beginning of conditioning regimen (9 days before stem cell infusion). All patients receive a total does of 0.4g/kg of intravenous γ globulin (IVIg) within 72 hours before stem cell administration to neutralize the remaining DSA. Protocols are showing as Figure 1A. Results: The maximal DSA level of one loci of HLA is calculated as follows. The mean baseline DSA levels before desensitization were 12232 MFI (SD 5358, range 4571~20114). Five (38.5%), 7(92.3%), and 1(7.7%) patients with DSA levels <10000,1000 to 20000, and >20000 MFI, respectively. The patient with DSA>20000MFI had antibody only against class I HLA antigens. The mean DSA level after desensitization was 7872MFI (SD6078, range784~18703), which was significantly lower in contrast to predensensitization levels (P= 0.001475). All patients achieved neutrophil engraftment and 12 patient achieved platelet engraftment in the first month post HaploSCT. The median engraftment of neutrophil is 14(range 10~21) days post-transplant. The median platelet engraftment is 15（range 8~372) days post-transplant. The patient with primary platelet engraftment failure received purified CD34 positive stem cell infusion 1 year after transplantation and achieved platelet engraftment thereafter. Figure 1B Figure 1 C.The estimated 1 and 3 year-overall survival (OS) is 73.4% (Figure 1D), NRM at 1 year for all patients was 26.6%, 2 patients were lost all due to acute graft versus host disease and subsequent infection. Summary/Conclusion:We here retrospectively report an positive result of DSA desensitization and successful engraftment using combination of only rituximab and IVIG. DSA should be monitored before and after desensitization treatment, All patients with positive MFI are recommended to receive treatment. Repeated DSA levels should be considered after treatment or before infusion of stem cell. It seems not necessary to receive HSCT until the MFI reaches negative, for the reason that the DSA levels will not clear immediately after treatment or infusion of stem cell. Although further studies on larger numbers are needed, it is clear that combination of IVIG and rituximab is an effective way to clear DSA and has a strong effect on promoting the engraftment and survival for patients with DSA. Figure 1Keywords: Haploidentical stem cell transplantation, Rituximab, IVIg